The objective of this pilot project is to examine whether arylhydrocarbon receptor (AhR) activation inhibits androgen-dependent prostate cell growth by regulating retinoblastoma tumor suppressor protein (pRb) activity. Recent evidence suggests that AhR agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related polycyclic aromatic hydrocarbons, can suppress androgen (AR) activation and prostate cancer cell growth. pRb is a transcriptional coactivator for both the AhR and AR. Androgen signaling leads to up regulation of the cyclin-dependent kinases 2 and 4 responsible for cell cycle progression. TCDD signaling is known to increase the level of the cyclin-dependent kinase inhibitor, p27kip1, triggering cell cycle arrest. Both pathways affect pRb activity and identify pRb as a molecular target for crosstalk between AhR and AR signaling. The investigators hypothesize that the arylhydrocarbon receptor (AhR) inhibits androgen-dependent cellular proliferation by regulating retinoblastoma tumor suppressor protein activity in the LNCAP human prostate cell line. 1. To determine whether the AhR can inhibit androgen dependent prostate cell proliferation by regulating G1 cell cycle progression. Recent evidence suggests that AhR agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related polycyclic aromatic hydrocarbons, can suppress AR activation and prostate cancer cell growth. The effect of AhR agonists on the growth of the androgen-dependent LNCaP human prostate cancer cell line will be examined. LNCaP cell growth will be analyzed using flow cytometry, and p27kipl, cyclins D and E, and the cyclin dependent kinases 2 and 4. 2. To determine whether androgen-dependent cell growth in LNCaP cells can be regulated by controlling AhR function and the pRb protein level. Retinoblastoma tumor suppressor protein is a transcriptional coactivator for both the AhR and AR. Androgen signaling leads to up regulation of the cyclin dependent kinases 2 and 4 responsible for cell cycle progression. TCDD signaling is known to increase the level of the cyclin-dependent kinase inhibitor, p27kip1, triggering cell cycle arrest. Both pathways affect pRb activity and identify pRb as a molecular target for crosstalk between AhR and AR signaling. AhR activity will be regulated using dominant negative and antisense RNA strategies or by using AhR antagonists, and the effect on androgen-dependent LNCaP cell growth assessed. Crosstalk between the AhR and AR will be analyzed in LNCaP cells as a function of the pRb protein level by inducing ectopic pRb expression in LNCaP cells.